Abstract
The proper regulation of translation is required for the expression of long-lasting synaptic plasticity. A major site of translational control involves the phosphorylation of eukaryotic initiation factor 2 α (eIF2α) by PKR-like endoplasmic reticulum (ER) kinase (PERK). To determine the role of PERK in hippocampal synaptic plasticity, we used the Cre-lox expression system to selectively disrupt PERK expression in the adult mouse forebrain. Here, we demonstrate that in hippocampal area CA1, metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) is associated with increased eIF2α phosphorylation, whereas stimulation of early- and late-phase long-term potentiation (E-LTP and L-LTP, respectively) is associated with decreased eIF2α phosphorylation. Interesting, although PERK-deficient mice exhibit exaggerated mGluR-LTD, both E-LTP and L-LTP remained intact. We also found that mGluR-LTD is associated with a PERK-dependent increase in eIF2α phosphorylation. Our findings are consistent with the notion that eIF2α phosphorylation is a key site for the bidirectional control of persistent forms of synaptic LTP and LTD and suggest a distinct role for PERK in mGluR-LTD.
Original language | English |
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Pages (from-to) | 298-304 |
Number of pages | 7 |
Journal | Learning and Memory |
Volume | 21 |
Issue number | 5 |
DOIs | |
State | Published - May 2014 |
Keywords
- Analysis of Variance
- Animals
- Biophysical Phenomena / drug effects
- Biophysical Phenomena / genetics
- CA1 Region, Hippocampal / physiology*
- Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
- DNA-Binding Proteins / metabolism
- Electric Stimulation
- In Vitro Techniques
- Long-Term Synaptic Depression / drug effects
- Long-Term Synaptic Depression / physiology*
- Methoxyhydroxyphenylglycol / analogs & derivatives
- Methoxyhydroxyphenylglycol / pharmacology
- Mice, Transgenic
- Microtubule-Associated Proteins / metabolism
- Receptors, Metabotropic Glutamate / metabolism*
- Transcription Factors / metabolism
- eIF-2 Kinase / genetics
- eIF-2 Kinase / metabolism*
ASJC Scopus subject areas
- Neuropsychology and Physiological Psychology
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience